"Viruses are known to play an important role in many lymphoproliferative diseases in animal models. The role of viruses as pathogenetic agents in human malignant lymphoma and leukemia is less clear. Epstein-Barr virus (EBV) plays an important role in some human cancers such as Burkitt's lymhoma and nasopharyngeal carcinoma. Recently, EBV has been identified as a possible co-factor in other diseases, such as Hodgkin's disease, lymphomatoid granulomatosis, nasal angiocentric T/NK cell lymphoma, HIV-associated lymphoma, and post-transplant lymphoproliferative disease of both B and T cell derivation. We are studying the expression of EBV-associated genes in human lymphoproliferative disease, and exploring the role of gene deletion and/or mutation in pathogenesis. We are also studying the role of gene expression in the pathophysiology of EBV-associated lymphoproliferative disease. We have identifed a profile of EBV-induced chemokines which appear to be involved in the pathogenesis of EBV-associated tissue necrosis. This work also has led to the development of novel therapeutic approaches for EBV-associated lymphoproliferative disease, such as immunotherapy utilizing both immunotoxins and immunomodulators. Ongoing studies are designed to correlate patterns of EBV gene expression in HD, T and B cell lymphomas, and PTLD with patterns of IP-10 and Mig gene expression. Previous studies in a xenograph murine model have suggested a role of the EBV gene LMP-1 in the induction of IP-10 and Mig. We will also determine whether intratumor inoculations with recombinant IP-10 and Mig can induce tissue necrosis and vascular damage in human HD and PTLD tumors established subcutaneously in a xenograph murine model. We are investigating other novel chemokines involved in the pathophysiology of both Hodgkin's disease and T and B cell lymphomas."